PB1751: RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKAEMIA (R/R ALL) IN A SINGLE-CENTRE PAEDIATRIC POPULATION
Authors: Guadalupe Ferreira Gomes, Ines L Goncalves, Ana Carolina Freitas, Joaquin Duarte Calvete
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: ALL is the most common cancer in childhood. Around 85% of children can be cured after contemporary treatment protocols. Relapse is the most frequent cause of treatment failure and survival remains poor. Only 50% of children with relapsed ALL will survive long-term despite intensive chemo-radiotherapy, allogeneic hematopoietic stem cell transplantation (HSCT) and novel salvage regimens. Most ALL relapses occur in the first 2 years (y) after treatment and most often in the bone marrow (BM), either isolated or combined with an extramedullary (EM) site, typically the central nervous system (CNS) or the testes. The most important prognostic factors at 1st relapse are time from diagnosis, site of relapse, immunophenotype, disease genetics and minimal residual disease (MRD) after reinduction therapy. Aims: To characterize a single-centre paediatric population with R/R ALL. Methods: Single-centre retrospective analysis of paediatric R/R ALL patients, including clinical features, treatment, response, and outcomes. All data was collected from clinical records and analysed with IBM SPSS 25.0. Results: A total of 82 children with R/R ALL diagnosed between 2008 and 2021 were identified. Here we report the first 33 patients with complete data reviewed. Median age at diagnosis was 8y and 70% (23/33) were male. All underwent intensive chemo-radiotherapy regimens in front-line. Most (88%; 29/33) achieved a complete remission after induction (CR1). Refractory disease was observed in 12% (4/33) of the children. In patients achieving CR1, positive MRD was detectable by molecular techniques in 21% (6/29). Very early relapses (<18 months (M) from diagnosis) were observed in 28% (8/29), early relapses (18-30M) in 10% (3/29) and late relapses (>30M) in 62% (18/29). Most were isolated BM relapses (69%; 20/29). The most frequent EM site affected was the CNS (14%; 4/29) followed by the testes (7%; 2/29). Relapsed patients had a probability of 2y overall survival (OS) of 53%, with a median follow-up time (FU) of 28M. 2y OS for refractory patients was 100% with a median FU of 85M. B-cell relapses had a 2y event free survival (EFS) of 61% and OS of 70%, while T-cell relapses had a 2y EFS and OS of 13% (p = 0.001). Very early relapses had a 2y EFS and OS of 0% (median EFS of 3M and OS of 5M) compared to 64% and 70%, respectively, in late relapses (p<0.001). BM relapses had a 2y EFS of 52% compared to 40% for EM relapses (combined or isolated) (p>0.001). High risk relapses had a 2y EFS 8% and 2y OS of 13%, compared to standard risk 2y EFS of 75% and OS of 82% (p<0.001). Most deaths were due to primary disease progression (67%; 10/15). Over half of the 1st relapses (59%; 17/29) had indication for HSCT, 24% (4/17) were ultimately transplanted. After HSCT 2y EFS was 75% and OS 100%, with a median FU of 58M. 2nd relapses were observed in 18% (10/29) of patients. Salvage treatments included intensive chemo-radiotherapy with immunotherapies, such as CAR-T cell (2/10), being incorporated in recent years. Summary/Conclusion: Survival rates among relapsed patients in our R/R cohort were in line with those previously published. B-cell ALL and late relapses were associated with better outcomes and HSCT provided long survival. All refractory patients survived in this cohort, and most were transplanted. Refractory disease criteria are currently under discussion and redefined in newer protocols. Treatment of R/R ALL remains deeply challenging. There is an unmet need for better and less toxic treatments. Novel immunotherapies are increasingly incorporated into salvage treatments to improve survival for children with R/R ALL. Keywords: Children, Acute lymphoblastic leukemia, Allo-SCT, Relapsed acute lymphoblastic leukemia